The Cleveland Clinic Foundation Musculoskeletal Core Center (CCFMCC). In the years since the original RFA for MCCs, musculoskeletal research activities have dramatically increased at CCF by the recruitment of Dr. Joseph Lannotti (an outstanding clinical musculoskeletal researcher) to the Chair of the Department of Orthopaedic Surgery, by the recruitment of Dr. Peter Cavanagh (an outstanding musculoskeletal biomechanics researcher) to the Chair of the Department of Biomedical Engineering, by the creation of the Orthopaedic Research Center in these two Departments, and by the recruitment of 3 new investigators into the Center. This, combined with an already strong musculoskeletal program, now provides a broadly based, interactive and well-funded Research Base for our proposed CCFMCC. Investigators in the Research Base currently are PIs on 14 NIH R01 grants, 9 of them funded by NIAMS. This clearly demonstrates the commitment of the CCF and NIH to this research. The ORC is committed to collaboration in translational research and enrichment programs. An example is the monthly Musculoskeletal Research Seminar Series that extends to Case Western Reserve University, University Hospitals Research Institute and NE Ohio Universities College of Medicine to generate synergistic research in the wider NE Ohio area. We ask, in this proposal, for funds to invite 4 national/international musculoskeletal researchers a year to enrich this already established activity. The CCFMCC would also enrich the research of the Center and CCF with 3 proposed cores: Musculoskeletal Imaging, Musculoskeletal Histology, and Musculoskeletal Robotics and Mechanical Testing, each with highly skilled Directors and Associate Directors. The imaging core was rated outstanding in our first submission and has added significantly to its resources, including microCT capabilities. The expansion of the Research Base has greatly increased the need for histology of soft and mineralized tissues and for in situ hybridization. The histology core would meet this need with high throughput, reproducible methods, particularly for tissue arrays, tissue sections and highly sensitive, non-radioactive in situ hybridization. Dr. Cavanagh has established a robotics system that, with our existing materials testing capabilities, forms the biomechanics core, adding a new and exciting dimension to investigations in the Research Base. An External Advisory Board of 5 outstanding musculoskeletal researchers has been assembled to review the Pilot and Feasibility Projects and for evaluating their progress on a yearly basis. Their stringent review of the 6 Projects prepared from the 13 originally proposed has led to the 2 that are incorporated into this application. In sum, we feel that we have all the necessary attributes to provide a highly competitive application for a MCC that would enhance our research in ways that can make a difference and contribute more significantly to musculoskeletal research.